LCZ696 is known as Sacubitril/Valsartan trisodium hemipetahydrate and chemically known as 3-[N-[1(S)-(biphenyl-4-ylmethyl)-4-ethoxy-3(R)-methyl-4-oxobutyl]carbamoyl]propionic acid and N-pentanoyl-N-[2′-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-L-valine trisodium hemipentahydrate and has the following structure, wherein designated as Formula-I.

Sacubitril is a neprilysin inhibitor pro-drug (AHU-377) and has now been tested in hypertension. LCZ696 has been approved in US under the trade name Entresto® as a tablet having dosage strengths 24 MG, 26 MG; 49 MG, 51 MG and 97 MG, 103 MG for treating chronic heart failure.
Pharmaceutical composition comprising Sacubitril or its pharmaceutically acceptable salt thereof and Valsartan or its pharmaceutically acceptable salt thereof is disclosed in U.S. Pat. No. 7,468,390 B2.
Mixed crystal/Co-crystal form of Sacubitril/Valsartan trisodium hemipentahydrate has been disclosed in U.S. Pat. No. 8,877,938 B2 of Novartis Pharmaceuticals. US′938 discloses the synthesis of Co-crystal of Sacubitril/Valsartan trisodium hemipentahydrate, which is as shown in FIG. 4.
US'938 also discloses the synthesis for Linked pro-drug of amorphous form of Sacubitril/Valsartan, which is as shown in FIG. 5.
CN 105693543 A discloses Sacubitril salts, wherein salt is selected from potassium salt, magnesium salt, t-butylamine salt, ethanolamine salt, piperazine salt, calcium, triethanolamine salt, trimethylamine salt.
CN 105461647 A discloses the Crystalline Form A of Sacubitril/Valsartan trisodium and Amorphous Forms α, β & γ of Sacubitril/Valsartan trisodium salt.
U.S. Pat. No. 7,468,390 B2 discloses the Triethanolamine and Tris(hydroxymethyl)aminomethane salts of Sacubitril.
The crystalline and amorphous form of Sacubitril/Valsartan sodium salt (LCZ696) were known, however still there is a need in prior-art to have a commercial, economical process to prepare stable amorphous form of the compound.
The present inventors have found a process for the preparation of amorphous form of Sacubitril/Valsartan sodium salt, wherein prepared. Amorphous form of Sacubitril/Valsartan sodium salt is stable, suitable for pharmaceutical formulation and is commercially, economically suitable for industrial scale.
Objectives
The objective of the present invention is to provide a process for the preparation of amorphous form of Sacubitril/Valsartan sodium salt, which is stable and has high yields and purity.
Another objective of the present invention is to provide a process for the preparation of amorphous form of Sacubitril/Valsartan sodium salt, which is commercially, economically suitable for industrial scale.